The goal of the Specialized Center of Research (SCOR) in Rheumatoid Arthritis (RA) at the Duke University Medical Center is to identify key steps in the pathogenesis of synovial inflammation and develop new approaches for treatment. This SCOR will unite a multidisciplinary group of clinical and basic scientists in a program of investigation that builds on past research accomplishments in RA and incorporates innovative approaches to probe the molecular basis of synovial inflammation. This program will utilize tissues and cells from patients with RA as well as animal models of arthritis to elucidate disease pathogenesis. The proposed SCOR will have 4 projects and 2 cores. Project 1 will focus on the role of CD44 in mediating adhesive interactions in synovitis and the contribution of CD7 negative T cells in promoting synovial inflammation. Project 2 will focus on the proinflammatory mediator nitric oxide and delineate the cytokines and mechanical factors that lead to upregulation of inducible nitric oxide synthase. Project 3 will elucidate the role of adhesion molecules in synovial inflammation by the study of the expression of selectins and integrins in murine models of arthritis, including backcross mice in which expression of selected adhesion molecules has been eliminated by gene targeting. Project 4 will focus on chemokines and chemokine receptors and delineate the changes in adhesion molecule function resulting from chemokine-induced activation. Two cores will support this research. A tissue culture and monoclonal antibody- core will provide synovial samples from patients with RA for cellular analysis; this core will also provide monoclonal antibodies for characterization of cell populations in the joint and peripheral blood. The administrative core will oversee all scientific and budgetary aspects of the center and assure strong programmatic focus. By amalgamating a talented team of investigators and focusing sharply on key events in the rheumatoid joint, the SCOR will accomplish its goals of delineating pathogenesis and promoting new treatment.